HLA haplotype diversity in the South Indian population and its relevanceLeenam Dedhia, Shruti Gadekar, Pooja Mehta, Sunil ParekhOctober-December 2015, 9(4):138-143DOI:10.1016/j.ijt.2015.10.016

Background: South India (SI) is the area encompassing India's states of Andhra Pradesh, Karnataka, Kerala, Telangana, and Tamil Nadu as well as the union territories of Lakshadweep and Pondicherry. South Indians are heterogeneous population with different ways of life, language, and physical appearance. A majority of Indians from the southern region speak one of the languages: Tamil, Telugu, Kannada, Malayalam, or Tulu. A large number of south-Indians have now migrated to different parts of the world and often need human leukocyte antigen (HLA) matched donors for treatment of different disorders. Knowledge of allele and haplotype frequencies of the HLA system is important in the search for unrelated bone marrow donors. The South Indian population is very heterogeneous and the HLA system is highly informative of populations because of the high level of polymorphisms. We investigated distribution of HLA A, B and DRB1 loci in five linguistic groups from SI.
Materials & methods: All the data were collected from the Marrow Donor Registry India (MDRI) which has pool of volunteer stem cell donors from these linguistic groups. DNA extracted from EDTA-blood sample of recruited donors, and HLA typing done using Luminex XMAP technology and sequence specific primer (SSP) technique at low–intermediate resolution. Graph pad InStat 3 and the software from National Marrow Donor Program (NMDP) were used for determining p values and haplotype frequency respectively.
Results: MDRI donors belonging to these five linguistic groups namely Tamil, Telugu, Tulu, Kannada, and Malayalam speaking donors were analyzed. The most common haplotypes were A*01-B*57-DRB1*07, A*33-B*44-DRB1*07, A*02-B*40-DRB1*15, A*24-B*07-DRB1*15, A*24-B*40-DRB1*15. A few unique haplotypes were seen as most common haplotype in each linguistic group.
Conclusion: Each linguistic group has unique haplotypes along with a few common haplotypes. In order to adequately represent the Indian population on the registry, each linguistic group should be targeted for donor recruitment. This would enable a better chance for any patient to find a matched unrelated donor.

Tuberculosis (TB), especially in developing countries like India, is a common infective complication after renal transplant with occurrence common in first 2 years. However, sternal TB is rare. We describe a 55-year-old female patient who after 5 years of live donor renal transplant with stable immunosuppression and graft function presented with a chest swelling and a destructive bony lytic lesion diagnosed as sternal TB with radiological and microbiological investigations. She was successfully treated with antitubercular therapy to which she spontaneously responded. This case, to the best of our knowledge, is the first reported case of sternal TB in a renal allograft recipient to be successfully managed with antitubercular therapy.

Thrombotic microangiopathy (TMA) is a clinical condition resulting from severe endothelial damage and leading to microangiopathic hemolytic anemia, consumptive thrombocytopenia, and ischemia of distal organs. TMA does not only develop in the native kidney but also appears as a recurrent or de novo condition in the transplanted kidney.
Etiology of de novo TMA includes renal ischemia, antibody-mediated rejection, malignancies, viral infections (CMV, parvovirus B19, BK polyomavirus, and HHV-6), antiphospholipid antibodies, anticardiolipin antibodies developing in HCV-positive patients, and medications (calcineurin inhibitors, m-TOR inhibitors, and antiviral medications).
Early diagnosis and treatment of TMA can be lifesaving. In this report, we present our experiences of successful treatment of a renal transplant case of TMA due to BK virus, not a frequent cause of TMA. The clinical picture of TMA caused by endothelial damage through cytopathic effects of viral antigens was evaluated in the light of the relevant literature.

Aims: To evaluate the nature and incidence of neurologic complications in recipients of living donor renal transplantation. Neurologic complications are a significant cause of morbidity and mortality in patients who undergo transplants and there is paucity of data regarding the same. The epidemiology of infective agents varies according to geographical locations.
Methods: We included 856 patients of live related renal transplantation at our institution between January 2002 and December 2009. All recipients who were found to have some clinical, laboratory, or radiological evidence of neurological involvement were considered. Associated comorbid medical conditions, presenting neurologic symptoms, and type of immunosuppression were recorded. Occurrence of acute rejections, chronic allograft nephropathy (CAN), delayed graft function, and new onset diabetes after transplant (NODAT) were recorded.
Results: Of the total 856 renal transplant recipients, a total of 93 (10.8%) patients were found to have some clinical, laboratory, or radiological evidence of neurological involvement. A total of 69 (73.3%) developed CNS complications with a mortality rate of 37.7%. CNS infections occurred in 47 (5% of total) recipients and accounted for the largest group (68.1%). Fungi were the commonest etiological agents, 22 (46.8%), and were associated with 40% mortality. Cryptococcal meningitis was occurring in 19 (27.5%), with mortality in 31.6% of these. Other fungal infections were aspergillosis in two and mucormycosis in one. All patients with aspergillosis and mucormycosis had a fatal outcome. The second largest group on CNS complications comprised of patients with cerebrovascular accidents, which occurred in 13 patients (18.8%), and were associated with a mortality of 23%. Eight patients with ischemic stroke had survived. Two had hemorrhagic stroke and both had a fatal outcome. Three patients had subdural hematoma with 33.3% mortality. Four patients had toxic encephalopathy as a result of fulminant systemic sepsis with mortality in all. Other less common CNS complications included intracranial space occupying lesion in two, postoperative psychosis in two, and hypoglycemic coma in one. There was no relationship between the development of infection or stroke and the type of maintenance immunosuppression used. A total 61 (65.5%) patients, which comprises 7% of the total transplant recipients, presented with some complications involving the peripheral nervous system (PNS). The most common manifestations were tremor in 26.5%, followed by paresthesias in 18.3%, steroid-induced myopathy in 11.8%, ulnar neuropathy in 4.4, and femoral neuropathy in 2.2%. These complications were more common with tacrolimus.
Conclusion: We conclude that complications involving the neurological system occur in 10.5% of all transplant patients with 8% involving CNS and 7% involving the PNS. The high mortality rates associated with CNS complications warrant early diagnosis and aggressive treatment in renal transplant recipients.

Role of ficolin-3 in acute kidney graft rejection: A new diagnostic toolFateme Shamekhi AmiriOctober-December 2015, 9(4):164-167DOI:10.1016/j.ijt.2015.10.017

The complement system has been implicated in a variety of conditions: autoimmune diseases, sepsis, transplantation, ischemia-reperfusion injuries, traumatic brain injury, infections, and bone biology. Complement activation in kidney transplantation may also induce allograft injury and contribute to delayed graft function. Activation of the complement system leads to the formation of molecules with proinflammatory properties. This may result in the killing of microorganisms, or it may lead to attack of altered self-tissue. The complement system may be activated through either of the three ways; that is, classic, alternative, and lectin pathways. The lectin pathway is initiated by binding of the pattern recognition molecules mannose-binding lectin or the three ficolins (ficolins 1, 2, 3) to the surfaces of pathogens or altered self-cells. It appears that a dual role of ficolin 3 may be present; while one being beneficial, the other be unfavorable effect, which does not result in bacterial or cellular clearance, but may lead to uncontrolled complement activation, resulting in adverse effects on the host. Research group demonstrated that decreased serum ficolin-3 was independently correlated with insulin resistance, and low serum ficolin-3 predicted the development of type 2 diabetes mellitus. Contrastingly, several studies showed that ficolin-3 might be one of the initiating factors involved in kidney rejection.

Background: Calcineurin inhibitor withdrawal with introduction of mammalian target of rapamycin inhibitors is associated with improvement in the renal function. The aim of the study was to evaluate the long-term allograft function after a complete switch over to everolimus from CNI at different time points.
Methods: Single center prospective, observational, follow-up study, in which 136 renal transplant patients received everolimus or continued CNI based therapy in de novo (day zero of transplantation), switch early (<6 months) and late (>6 months) groups. Patients were followed for 108 months.
Results: 88 patients completed the 108-month study. At month 108, the mean mGFR was 33.94 (95% CI 42.67–57.25) ml/mt/1.73 m2 in de novo group, 49.19 (95% CI 55.29–64.99) ml/mt/1.73 m2 in early switch over, 25.95 (95% CI 34.34–7.38) ml/mt/1.73 m2 in late switch over and 34.54 (95% CI 41.57–54.06) ml/mt/1.73 m2 in CNI group. Patient and graft survival were comparable among groups (p = 0.698). There were 5 (13.1%) deaths in the de novo, 3 (10.3%) in early switch, 5 (21.7%) in late switch, and 6 (13%) in CNI group. Biopsy proven acute rejection rates were comparable among the groups: 28.9%, 20.7%, 26.7%, and 19.5% in de novo, early, late and CNI groups respectively (p = 0.057).
Conclusion: Improvement in the renal function was observed in early switchover. Furthermore, patients with good renal function may benefit from conversion even at a late stage, and in patients with suboptimal renal function everolimus may not add any further benefit.

Antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) is a common cause of rapidly progressive glomerulonephritis resulting in end-stage renal disease (ESRD). Wegener's granulamotosis (WG) is a rare disease of this group that have granulomatosis with polyangiitis, characterized by a triad of necrotizing granulomas in the upper and lower respiratory tracts, small vessel vasculitis, and glomerulonephritis. This case report illustrates the various concerns implicated in the anesthetic considerations of a patient of ESRD with Wegener's granulomatosis for renal transplant.

We report first successful allogenic hematopoetic stem cell transplant of adult male with leukocyte adhesion deficiency. This patient was symptomatic for recurrent pyoderma gangrenosum since 10 years. He had received local treatments, systemic antibiotics, steroids, and cyclosporin but pyoderma was refractory leading to delay in hematopoetic stem cell transplant. The graft source was peripheral blood from 6/6 matched sibling. The conditioning regimen used was Busulphan, Cyclophosphamide, and antithymocyte globulin. Neutrophil engraftment occurred on day +14 and platelet engraftment occurred on day +24. Chimerism study of day +30 with VNTR showed 100% donor chimerism with normalization of CD18 expression.